Trichophyton mentagrophytes and Candida albicans are the two most common fungi which infect human toenail and fingernail tissue and are responsible for the vast majority of nail infections, medically termed onychomycosis, in the United States. The present inventor knows of no effective topical medication which is currently approved by the FDA and available for the treatment of such fungal infections.
Griseofulvin is a cream powder produced by Penicillium griseofulvum and has the formula C.sub.17 H.sub.17 O.sub.6 Cl. The griseofulvin molecule has a heterocyclic nucleus and a spyran ring junction. It is widely used as an oral antimycotic for many disease conditions. It is effective against Trichophyton mentagrophytes but is absorbed slowly after ingestion and thus does not provide high blood serum concentrations. Therefore, lengthy treatment periods are required. Griseofulvin is toxic to the liver and requires medical supervision. As a consequence, griseofulvin is not suitable for over-the-counter use.
Griseofulvin is available in tablet or capsule form by prescription to be orally administered for the treatment of Trichophyton mentagrophytes. Unfortunately, it requires a lengthy treatment time of between six months and several years and entails continuous, expensive therapy. Griseofulvin has been considered completely ineffective against fungal infections caused by Candida albicans.
Furthermore, griseofulvin is only slightly soluble in water and is poorly absorbed by skin and nail tissue. Previous attempts to provide a non-toxic, effective topical medication of griseofulvin have been unsuccessful. Compositions of griseofulvin dissolved in many aprotic solvents have been unsuccessful because the resultant solutions are toxic or exhibit other properties which severely limit their effectiveness and applicability. For example, two particular aprotic solvents are dimethyl sulfoxide (DMSO) and dimethyl formamide (DMF). DMSO and DMF can be used as solvents for griseofulvin and enable griseofulvin to penetrate skin and keratinous tissue. However, both of these solvents are toxic compounds. In fact, DMSO was generally taken off the market for medicinal use by the U.S. Food and Drug Administration years ago. No other permeation enhancers have been found to be effective in moving griseofulvin into skin and keratinous tissue. Also, none of the known and tested permeation enhancers exhibit any substantial effectiveness against Candida albicans.
Cinnamic aldehyde (PhCH:CHCHO, also known as cinnamaldehyde or .beta.-Phenylacrolein) has been considered a popular flavoring agent and aromatic agent. The solubility of cinnamic aldehyde in alcohol is known from Table C-233 of Handbook of Physics and Chemistry, 65th ed., from CRC Press (1984-1985). The present inventor presently knows of no previous antimycotic use of cinnamic aldehyde and of no packaged product comprising a sealed container having a solution of cinnamic aldehyde and alcohol therein.
Cinnamic aldehyde is the major ingredient in the natural plant oil--oil of cinnamon--which has been used as a folk remedy for the treatment of painful teeth and gums. It is also used as an itch remedy. Cinnamic aldehyde is on the U.S. Food and Drug Administration's list of agents which are "generally recognized as safe", that is, the GRAS list. Although there are aldehydes with antimicrobial activity, such as the familiar embalming fluids formaldehyde and glutaraldehyde, these latter two are particularly toxic to human tissue and cannot be safely used as medications.
A need therefore exists for a non-toxic antifungal composition which can be topically applied and is effective against infections of both Trichophyton mentagrophytes and Candida albicans. A need also exists for a topical composition which provides adequate solration of griseofulvin, an enhancement in permeation and penetration of griseofulvin into keratinous tissue, and a stable shelf life.